1. Department of Zoology, University of Toronto, Toronto, Ontario M5S 3G5, Canada
2. The Hospital of Sick Children, Arthur and Sonia Labatt Brain Tumor Research Center, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada
3. Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47906, USA
4. These authors contributed equally to this work

Correspondence to: Correspondence and requests for material should be addressed to U.T. (e-mail: Email: utepass@zoo.utoronto.ca).

Abstract

The apical transmembrane protein Crumbs is a central regulator of epithelial apical–basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical–basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies.

1. Department of Zoology, University of Toronto, Toronto, Ontario M5S 3G5, Canada
2. The Hospital of Sick Children, Arthur and Sonia Labatt Brain Tumor Research Center, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada
3. Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47906, USA
4. These authors contributed equally to this work

Correspondence to: Correspondence and requests for material should be addressed to U.T. (e-mail: Email: utepass@zoo.utoronto.ca).